The goals of this project are to characterize the pathogenesis, natural history and therapy of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Our clinical emphasis has been on oral and genital herpes and zoster in the normal and the immuno-compromised host. Over the years we established the value, long term efficacy and safety of oral acyclovir for suppression of recurrent genital herpes and more recently oral herpes as well. We initiated collaborative studies of BVaraU, a new drug for zoster. Also in the past year, we studied and reported the first known instance of a persistent acyclovir-resistant HSV2 infection in an immunologically normal individual. The major basic research thrust of this laboratory has been to define molecular aspects of SHV and VZV latency and pathogenesis. We are examining the role of the HSV I and II latency-associated transcripts (LAT) in control of virus latency and reactivation. Recombinant viruses deleted for LAT expression are being studied in vitro and in animal models. We have begun to create transgenic mice expressing HSV genes neighboring and/or including the LAT gene. We are also studying specific LAT promotor elements. Work on VZV latency and gene regulation has concentrated on genes 4, 10, 28, 21, 61, 62, and 63. Because gene 29 is expressed in latency and 28 is not, we are studying the regulation of these two genes. We found that they share a common expression of both genes.